Table 1 Enantioselective hydrogenation of ethyl pyruvate over a 5% Pt/
Al catalyst (Engelhard 4759) in AcOH at room temperature [50 mg of
alkaloids(closed)–EtPy complex is not a precondition for chiral
induction. On the other hand, extensive studies with respect to
cinchona-modified pyruvate hydrogenation in AcOH, accom-
panied by the present results, strongly supports the 1:1
adsorptive interaction model7 of Baiker, Blaser and co-
workers. In neutral solvents, the recently revised mechanistic
proposal by Wells17 and co-workers seems most likely.
2 3
O
catalyst (as received), 5 mg of modifier, 5 ml of solvent and 0.25 ml of ethyl
a
pyruvate]
,8
Ee (%)
Modifier
2
H pressure/bar Conversion (%) (configuration)
CD
CD
CN
CN
ICN
ICN
a
1
50
1
50
1
50
100
100
95
98
94
80 (R)
90 (R)
72 (S)
67 (S)
67 (S)
69 (S)
Our results obtained with ICN suggest further mechanistic
studies of cinchona-modified asymmetric syntheses utilising
other cinchona alkaloids of rigid conformation. The results of
24
this work provide further proof of our earlier statement that
the conformation of the reactants is of crucial importance in
determining the selectivity of metal-catalyzed transforma-
tions.
Financial support by the Hungarian National Science Foun-
dation (OTKA Grant T016109) and the Hungarian Academy of
Sciences (AKP 97-4 2,4) is highly appreciated. Our most
sincere thanks are due to Dr J. Thiel (A. Miczkiewicz
University, Poznan, Poland) for the donation of the a-
isocinchonine sample used to start these investigations.
98
Analysis: ee (%) = 100{[R] 2 [S] (or [S] 2 [R])}/([R] + [S]), chiral
GC (HP 5890 GC-FID, 30 m long Lipodex-A column), HPLC-MS (HP1090
Ser.II HPLC-HP5989B MS with an HP5987A ES interface).
conformations of CN [Fig 2(a)] and ICN [Fig. 2(c)] alkaloids
suggested and verified by combined NMR and X-ray analysis
and molecular mechanical calculations.2
0–22
Conformational
changes in CN are possible by rotation along the C(4A)–C(9) and
C(8)–C(9) bonds. [It should be noted that in the case of flat
Notes and references
1 Catalytic Asymmetric Synthesis, ed. I. Ojima, VCH, Weinheim, 1993.
adsorption of the quinoline skeleton on platinum, as already
pointed out,1
7,23
the C(4A)–C(9) rotation is hindered.] To realize
2
R. Noyori, Asyymmetric Catalysis in Organic Chemistry, Wiley, New
York, 1994.
our aim mentioned above, ICN was selected because it cannot
rotate around C(8)–C(9). It is also known that ICN exists only
in ‘anti-open’ conformation.22
3
4
5
6
H. U. Blaser, Tetrahedron: Asymmetry, 1991, 2, 935.
H. U. Blaser and M. Müller, Stud. Surf. Sci. Catal., 1991, 59, 73.
R. A. Sheldon, Chirotechnology, Marcel Decker, New York, 1993.
Chiral Reactions in Heterogeneous Catalysis, ed. G. Jannes and V.
Dubois, Plenum, New York and London, 1995.
The enantioselective hydrogenation of ethyl pyruvate (EtPy)
was performed either in a conventional atmospheric hydro-
genation apparatus or in a Berghof Bar 45 autoclave at room
temperature (25 °C). The results are shown in Table 1.
As the HPLC–ESMS measurements revealed, the ICN
modifier did not revert back to CN, i.e. the cyclic ether structure
remained stable during the hydrogenations. As the results
clearly show the ICN modifier of fixed conformation showed
practically the same performance (conversion, ee) as CN during
the hydrogenations.
7 A. Baiker, J. Mol. Catal. A: Chem., 1997, 115, 473 and references cited
therein.
8
9
H. U. Blaser, H. P. Jalett, M. Müller and M. Studer, Catal. Today, 1997,
7, 441 and references cited therein.
H. U. Blaser and H. P. Jalett, J. Mol. Catal., 1991, 68, 215.
3
1
0 B. Török, K. Felföldi, G. Szakonyi, K. Balázsik and M. Bartók, Catal.
Lett., 1998, 52, 81.
1
1 M. Schürch, T. Heinz, R. Aeschimann, T. Mallatt, A. Pfaltz and A.
Baiker, J. Catal., 1998, 173, 187.
The proposed intermediate complex of the chiral hydro-
genation carried out in the presence of ICN is illustrated in
Fig. 3. It should be mentioned that only the existence of the
12 Y. Orito, S. Imai and S. Niva, J. Chem. Soc. Jpn., 1979, 1118.
13 K. Ito, T. Harada, A. Tai and Y. Izumi, Chem. Lett., 1979, 1049.
14 R. L. Augustine and S. K. Tanielyan, J. Mol. Catal. A: Chem., 1996,
anti-open’ conformer was proven in solution;22 the formation
‘
1
12, 93.
of the ‘syn-open’ conformer during the adsorption cannot be
excluded.
1
5 A. Baiker and H. U. Blaser, Handbook of Heterogeneous Catalysis, ed.
G. Ertl, H. Knözinger and J. Weitkamp, Wiley-VCH, Weinheim, 1997,
vol. 5, p. 2422.
These experimental data strongly support the existence of the
structures in Fig.1(b) and (c) when working under acidic
conditions. Further measurements are necessary, however, to
distinguish between the two structures. Although the reaction
conditions are not fully optimized in the case of CN and ICN it
is unambiguously proven that the formation of a cinchona
1
6 H. U. Blaser, H. P. Jalett, M. Garland, M. Studer, H. Thies and A. Wirth-
Tijani, J. Catal., 1998, 173, 282.
1
7 K. E. Simons, P. A. Meheux, S. P. Griffiths, I. M. Sutherland, P.
Johnston, P. B. Wells, A. F. Carley, M. K. Rajumon, M. W. Roberts and
A. Ibbotson, Recl. Trav. Chim. Pays-Bas, 1994, 113, 465.
8 J. L. Margitfalvi, M. Heged u¯ s and E. Tfirst, Stud. Surf. Sci. Catal., 1996,
1
1
1
01, 241.
OEt
9 J. L. Margitfalvi, E. Tfirst, M. Heged u¯ s and E. Tálas, 17th Conference
on Catalysis of Organic Reactions, ed. F. E. Herkes, New Orleans,
L. A., March 29–April 2, 1998, Pre-Prints, Poster 5.
OEt
C
O
C
N
H
O
C
C
H
N
H
R
O
Me
Me
R
H
O
Me
R
20 G. D. H. Dijkstra, R. M. Kellogg, H. Wynberg, J. S. Svendsen, I. Marko
and K. B. Sharpless, J. Am. Chem. Soc., 1989, 111, 8069.
21 G. D. H. Dijkstra, R. M. Kellogg and H. Wynberg, J. Org. Chem., 1990,
55, 6121.
Me
R
H
O
S
H
O
S
N
N
22 J. Thiel and P. Fiedorow, J. Mol. Struct., 1997, 405, 219.
2
2
3 G. Bond and P. B. Wells, J. Catal., 1994, 150, 329.
4 M. Bartók, Á. Molnár and J. Apjok, J. Catal., 1985, 95, 605.
(a)
(b)
Fig. 3 The structures of a-isocinchonine–ethyl pyruvate intermediate
complexes [(a) ‘anti-open’ complex, (b) ‘syn-open’ complex].
Communication 8/07039C
2606
Chem. Commun., 1998, 2605–2606